Sample manager, system, and method

Abstract

A liquid chromatography sample manager includes a sampling mechanism; a sample tray mounted in the sampling mechanism, the sample tray configured to rotate about a first vertical axis; a needle arm mounted within the sampling mechanism, the needle arm configured to rotate about a second vertical axis; and a sample delivery system in fluid communication with a solvent delivery system, the sample delivery system including a sample needle attached to the needle arm, the sample delivery system configured to transfer a first sample from a first sample vial holder located in the sample tray into a chromatography flow stream.

Description

[0001] Related applications

[0002] This application claims the benefit of the earlier filing date of U.S. Provisional Patent Application Serial No. 62 / 990,613 entitled “SampleManager, System and Method”, filed on March 17, 2020, the entire contents of which are incorporated herein by reference. Technical Field

[0003] This invention relates generally to liquid chromatography systems. More specifically, this invention relates to liquid chromatography sample managers and related systems and methods. Background Technology

[0004] Chromatography is a set of techniques for separating mixtures into their components. For example, in a liquid chromatography system, a pump draws in a mixture of liquid solvents and delivers it to a sample manager, where the injected sample awaits its arrival. In isocratic chromatography, the composition of the liquid solvent remains constant, while in gradient chromatography, the solvent composition changes over time. The mobile phase, consisting of the sample dissolved in the solvent mixture, is directed to a column called the stationary phase. By passing the mixture through the column, the various components in the sample separate from each other at different rates and thus elute from the column at different times. A detector receives the eluent from the column and produces an output from which the species and quantity of the analyte can be determined.

[0005] Before being supplied to the liquid chromatography system, the sample can be provided to the sample manager. The sample manager can be configured to prevent the sample from degrading or otherwise being damaged during its supply to the liquid chromatography system. Since the sample manager interacts regularly with technicians, it must be user-friendly, reliable, accurate, dependable, maintainable, and cost-effective. Improved sample managers, systems, and methods will be highly valued in the field. Summary of the Invention

[0006] In one embodiment, a liquid chromatography system includes: a solvent delivery system; a sample manager having a heat treatment chamber including: a sampling mechanism mounted within the heat treatment chamber, the sampling mechanism including: a sample tray mounted therein configured to rotate about a first vertical axis; a needle arm configured to rotate about a second vertical axis; and a sample delivery system in fluid communication with the solvent delivery system, the sample delivery system including a sample needle attached to the needle arm, the sample delivery system being configured to transfer a first sample from a first sample vial holder located in the sample tray into a chromatographic flow; a liquid chromatography column located downstream of the solvent delivery system and the sample delivery system; and a detector located downstream of the liquid chromatography column.

[0007] Additionally or alternatively, the sample manager includes a front door configured to load and unload sample vial holders into the sample tray, and the needle arm can be removed from the front door.

[0008] Additionally or alternatively, the needle arm includes a belt and pulley drive mechanism.

[0009] Additionally or alternatively, the heat treatment chamber also includes a motor operatively connected to a belt and pulley drive mechanism, wherein the motor is removable from the front door.

[0010] Additionally or alternatively, the needle arm includes a magnetic encoder configured to determine the rotational position of the needle arm.

[0011] Additionally or alternatively, the sample delivery system includes a fluid tube located between the sample needle and the liquid chromatography column, wherein the fluid tube includes a coiled portion configured to extend and retract during rotation of the needle arm.

[0012] Alternatively or additionally, the sample tray is circular and includes a first compartment, a second compartment, a third compartment, and a fourth compartment equidistantly arranged around the perimeter of the circular sample tray.

[0013] Additionally or alternatively, the liquid chromatography system also includes a control system configured to control the rotational movement of each of the sample disk and the needle arm. The control system is configured to control a calibration process comprising the following steps: moving the sample disk such that a first opening in the sample disk aligns with a sample needle on the needle arm; moving the needle arm above the aligned first opening and recording a first encoder position for each of the sample disk and the needle arm; moving the sample disk such that a second opening in the sample disk aligns with a sample needle on the needle arm; moving the needle arm above the aligned second opening and recording a second encoder position for each of the sample disk and the needle arm; and using the known first and second encoder positions, calculating the geometric parameters of the sample disk and the needle arm to calibrate the movement of the sample disk and the needle arm.

[0014] In another embodiment, a liquid chromatography sample manager includes: a heat treatment chamber; a sample tray mounted in the heat treatment chamber and configured to rotate about a first vertical axis; a needle arm mounted in the heat treatment chamber and configured to rotate about a second vertical axis; and a sample delivery system in fluid communication with a solvent delivery system, the sample delivery system including a sample needle attached to the needle arm, the sample delivery system being configured to transfer a first sample from a first sample vial holder located in the sample tray into a chromatographic flow.

[0015] Additionally or alternatively, the sample manager includes a front door configured to load and unload sample vial holders into a sample tray, wherein the needle arm is removable from the front door.

[0016] Additionally or alternatively, the needle arm includes a belt and pulley drive mechanism.

[0017] Additionally or alternatively, the heat treatment chamber also includes a motor operatively connected to a belt and pulley drive mechanism, wherein the motor is removable from the front door.

[0018] Additionally or alternatively, the needle arm includes a magnetic encoder configured to determine the rotational position of the needle arm.

[0019] Additionally or alternatively, the sample delivery system includes a fluid tube located between the sample needle and the liquid chromatography column, wherein the fluid tube includes a coiled portion configured to extend and retract during rotation of the needle arm.

[0020] Alternatively or additionally, the sample tray is circular and includes a first compartment, a support compartment, a support compartment, and a support compartment equidistantly arranged around the perimeter of the circular sample tray.

[0021] Additionally or alternatively, the sample manager includes a control system configured to control the rotational movement of each of the sample tray and the needle arm. This control system is configured to control a calibration process comprising the following steps: moving the sample tray such that a first opening in the sample tray aligns with a sample needle on the needle arm; moving the needle arm above the aligned first opening and recording a first encoder position for each of the sample tray and the needle arm; moving the sample tray such that a second opening in the sample tray aligns with a sample needle on the needle arm; moving the needle arm above the aligned second opening and recording a second encoder position for each of the sample tray and the needle arm; and using the known first and second encoder positions, calculating the geometric parameters of the sample tray and the needle arm to calibrate the movement of the sample tray and the needle arm.

[0022] Additionally or alternatively, the needle arm is configured to rotate at least 45 degrees about a second vertical axis, and the sample disk is configured to rotate 360 ​​degrees about a first vertical axis.

[0023] In another embodiment, the method for calibrating the sample manager includes: moving a sample tray such that a first opening in the sample tray aligns with a sample needle on a needle arm; moving the needle arm over the aligned first opening and recording a first encoder position for each of the sample tray and the needle arm; moving the sample tray such that a second opening in the sample tray aligns with a sample needle on the needle arm; moving the needle arm over the aligned second opening and recording a second encoder position for each of the sample tray and the needle arm; and using the known first and second encoder positions, calculating the geometric parameters of the sample tray and the needle arm to calibrate the movement of the sample tray and the needle arm. Attached Figure Description

[0024] The above and other advantages of the present invention can be better understood by referring to the following description in conjunction with the accompanying drawings, in which the same reference numerals indicate the same elements and features in each drawing. For clarity, not every element is labeled in every drawing. The drawings are not necessarily drawn to scale, but are intended to illustrate the principles of the invention.

[0025] Figure 1 A schematic diagram of a liquid chromatography system including a sample manager according to one embodiment is depicted.

[0026] Figure 2 The following is described according to an implementation scheme: Figure 1 A perspective view of the liquid chromatography system in the sample manager.

[0027] Figure 3 Depicting according to an implementation scheme Figure 1 and Figure 2 A perspective view of the inside of the sample manager.

[0028] Figure 4 The first calibration position is depicted according to one implementation scheme. Figure 1 and Figure 2 A perspective view of the inside of the sample manager.

[0029] Figure 5 The second calibration position is depicted according to one implementation scheme. Figure 1 and Figure 2 A perspective view of the inside of the sample manager.

[0030] Figure 6 A perspective view depicting a needle arm disassembled from the inside of a sample manager according to one embodiment is shown.

[0031] Figure 7 The disassembled needle assembly is depicted according to one embodiment. Figure 6 A perspective view of the needle arm.

[0032] Figure 8 Depicting according to an implementation scheme Figure 6 Side view of the needle arm.

[0033] Figure 9 Depicting according to an implementation scheme Figure 6 and Figure 8 A top view of the needle arm.

[0034] Figure 10 Depicting the implementation of an scheme in Figure 9 The arrow at point 10-10 is cut off. Figure 6 , Figure 8 and Figure 9 A side view cross-sectional view of the needle arm. Detailed Implementation

[0035] In this specification, references to "an embodiment" or "an embodiment" mean that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of this teaching. References to a particular embodiment within this specification do not necessarily refer to the same embodiment.

[0036] The teachings will now be described in more detail with reference to exemplary embodiments illustrated in the accompanying drawings. While the teachings have been described in conjunction with various embodiments and examples, they are not intended to be limited to such embodiments. In contrast, the teachings encompass various alternatives, modifications, and equivalents, as will be understood by those skilled in the art. Those of ordinary skill in using the teachings herein will recognize additional implementations, modifications, and embodiments, as well as other areas of use, within the scope of this disclosure as set forth herein.

[0037] As described herein, prior to performing a liquid chromatography run, a technician loads the sample-containing vial array onto a sample vial holder, places the sample vial holder onto a drawer, and slides the drawer into a compartment within the sample tray of the heat treatment chamber of the sample manager system. The sample manager system includes a sample delivery system configured to transfer samples from the sample vial holder into the chromatographic flow. The heat treatment chamber includes a sampling mechanism comprising a rotating sample tray with improved sample capacity and sampling accuracy. A sampling needle, as part of the sampling mechanism, is located on a rotating needle arm that, in conjunction with the rotating sample tray, provides complete needle coverage over the compartment within the sample tray. The entire needle arm is positioned and sized within the heat treatment chamber, allowing it to be removed from the front door of the heat treatment chamber for servicing. Encoders on the rotating needle arm and rotating sample tray maintain sufficient resolution for accurate sampling. These rotating needle arms can be calibrated using a calibration process that ensures accuracy.

[0038] The features of the sample delivery system and sample manager heat treatment chamber described herein can be applied to any liquid chromatography system configured to deliver samples to a chromatographic flow. As an example, Figure 1 An embodiment of a liquid chromatography system 10 for separating a mixture into its components is shown. The liquid chromatography system 10 includes a solvent delivery system 12 in fluid communication with a sample manager 14 (also referred to as a syringe or autosampler) via tubing 16. The sample manager 14 is in fluid communication with a chromatographic column 18. A detector 21, such as a mass spectrometer, is in fluid communication with the column 18 to receive the eluent.

[0039] The solvent delivery system 12 includes a pumping system 20 in fluid communication with a solvent reservoir 22, which draws solvent (liquid) from the reservoir via tubing 24. In one embodiment, the pumping system 20 is embodied in a low-pressure mixing gradient pumping system having two pumps fluidly connected in series. In the low-pressure gradient pumping system, solvent mixing occurs prior to the pumps, and the solvent delivery system 12 has a mixer 26 in fluid communication with the solvent reservoir 22 to receive various solvents in metered proportions. This mixing of the solvent (mobile phase) composition varies over time (i.e., gradient).

[0040] Pumping system 20 is in fluid communication with mixer 26 to draw a continuous gradient flow from it for delivery to sample manager 14. Examples of solvent delivery systems that can be used to implement solvent delivery system 12 include, but are not limited to, the ACQUITY binary solvent manager and the ACQUITY quaternary solvent manager manufactured by Waters Corp. of Milford, Mass.

[0041] Sample manager 14 may include syringe valve 28 having sample loop 30. Sample manager 14 operates in one of two states: loading state and injection state. In the loading state, the position of syringe valve 28 causes the sample manager to load sample 32 into sample loop 30. Sample 32 is withdrawn from a vial held by a vial holder. "Sample loop holder" as used herein refers to any device configured to carry a sample vial, such as a well plate, vial holder, etc. In the injection state, the position of syringe valve 28 changes, causing sample manager 14 to introduce the sample in sample loop 30 from the solvent delivery system into a continuously flowing mobile phase. The mobile phase then carries the sample into column 18. In other embodiments, a flow-through needle (FTN) sample manager may be used instead of a fixed-loop sample manager. Using the FTN method, the sample is pulled into the needle, which can then be moved into a seal. The valve can then be switched to align the needle with the solvent delivery system.

[0042] The liquid chromatography system 10 further includes a data system 34 that communicates with the solvent delivery system 12 and the sample manager 14. The data system 34 has a processor 36 and a switch 38 (e.g., an Ethernet switch) for handling the signal communication between the solvent delivery system 12 and the sample manager 14. Signal communication between the various systems and instruments can be electrical or optical, and can be performed using wireless or wired transmission. A host computing system 40 communicates with the data system 34, through which technicians can download various parameters and configuration files (e.g., inlet gas rate configuration files) to the data system 34.

[0043] Figure 2 A perspective view of a liquid chromatography system 10 is shown, which includes a sample manager 14, a detector 21, a column 18, a solvent delivery system 12, and a solvent 22. Each of the sample manager 14, detector 21, column 18, and solvent delivery system 12 may include a housing or body within which various features such as a data system 34, a sample loop 30 and syringe valve 28, a pumping system 20, a mixer 26, and tubing 24 may be housed. The various components 12, 14, 18, 19, 21, and 22 may interconnect with fluid tubing and communicate signalingly with the system's data system 34. The liquid chromatography system 10 is shown as having a solvent delivery system 12, a sample manager 14, a column 18, a detector 21, and a tray for holding the solvent 22 stacked together.

[0044] Figure 3 Depicting according to an implementation scheme Figure 1 and Figure 2 A perspective view of the sampling mechanism 100 of the sample manager 14. As shown, the sampling mechanism 100 includes a sample tray 110 attached to a reference base 112. A vertical frame 114 is attached and extends perpendicular to the reference base 112. A needle arm 116 is attached to the vertical frame 114. The needle arm 116 includes a puncture needle 122 (e.g., Figure 4 (as shown) and a sample needle (not shown) as part of a sample delivery system that is in fluid communication with a solvent delivery system 12. The sample needle can be configured to deliver the sample from a sample vial 33 (as shown). Figure 2 Sample 32 is obtained or otherwise extracted (as shown). Subsequently, the sample delivery system of the liquid chromatography system 10 is configured to transfer sample 32 into the chromatographic flow and to column 18 located downstream of the sample delivery system, and then to detector 21 located downstream of column 18. Sample vial 33 may be one of a plurality of vials located within up to four vial holders (not shown) on sample tray 110.

[0045] The sample tray 110 can be configured to rotate 360 ​​degrees about a first vertical axis A1, while the needle arm 116 is configured to rotate at least partially about a second vertical axis A2. These two rotations can provide sufficient coverage of all sample vial holders 124 within the sample tray 110 via the needle arm 116. The combination of rotating the needle arm 116 with the rotation of the sample tray 110 can thus be configured to move the sample needle 122 to a position close to any location on the sample tray 110 that holds the sample vial 33 within the sample vial holder.

[0046] As shown in the figure, the sample tray 110 includes a circular frame comprising four compartments – a first support compartment 126a, a second support compartment 126b, a third support compartment 126c, and a fourth support compartment 126d. The support compartments 126a, 126b, 126c, and 126d are equidistantly arranged around the periphery of the circular sample tray 110. In other words, the support compartments 126a, 126b, 126c, and 126d are arranged circumferentially 90 degrees to each other around the circular sample tray 110. As described above, the rotation of the rotating needle arm 116 in conjunction with the rotation of the sample tray 110 is configured to move the sample needle 122 directly over any position covered by the respective periphery of the respective support compartments 126a, 126b, 126c, and 126d. The tray may include the four compartments shown, but in other embodiments, it may also include three compartments or extend to even more than four compartments. The compartments may be equidistant from each other or may otherwise be staggered around the circumference of the circular sample tray 110.

[0047] Each of the support compartments 126a, 126b, 126c, 126d is shown as a drawer for sliding in and out of the compartment drawer receivers 128a, 128b, 128c, 128d. The support compartments 126a, 126b, 126c, 126d can be configured to be pulled radially outward from the respective compartment drawer receivers 128a, 128b, 128c, 128d to facilitate loading the sample vial holder into and out of the sample tray through the front door 130 (e.g., Figure 2 (As shown). The integration of support compartments 126a, 126b, 126c, 126d and corresponding compartment drawer receivers 128a, 128b, 128c, 128d can be configured to stop support compartments 126a, 126b, 126c, 126d from the compartment drawer receivers 128a, 128b, 128c, 128d before they are completely disconnected from the compartment drawer receivers 128a, 128b, 128c, 128d. Alternatively, the frame of the sampling mechanism 100 may include a structure to prevent the support compartments 126a, 126b, 126c, 126d from being completely disconnected from the compartment drawer receivers 128a, 128b, 128c, 128d.

[0048] Each of the four support compartments 126a, 126b, 126c, and 126d is configured to receive a sample vial holder. The sample manager 100 can be configured to receive and process samples within all four support compartments 126a, 126b, 126c, and 126d. In addition to sliding in and out of the compartment drawer receivers 128a, 128b, 128c, and 128d via a track system, each support compartment 126a, 126b, 126c, and 126d may include a lower magnet configured to magnetically hold the sample vial holder in place within the support compartment 126a, 126b, 126c, and 126d. The corresponding magnets can be located radially inward within the support chambers 126a, 126b, 126c, and 126d to further ensure that the support chambers 126a, 126b, 126c, and 126d are correctly positioned (i.e., fully inserted) relative to the chamber drawer receivers 128a, 128b, 128c, and 128d. The leaf spring 132 can be configured to bias the received sample tray toward the leftmost wall of the corresponding support chamber 126a, 126b, 126c, and 126d, while the magnetic structure holds the received sample tray against the radially inward wall of the corresponding support chamber 126a, 126b, 126c, and 126d.

[0049] The sample tray 110 includes a central opening 134 for receiving a post 136, and the sample tray 110 is configured to rotate about a vertical axis A1 about the post. The sample tray 110 also includes additional openings 136 arranged peripherally between support chambers 126a, 126b, 126c, and 126d, which are configured to receive and hold larger individual vials (not shown) or other samples. A needle arm 116 (and its needle) can be configured to be positioned above each of the peripheral additional openings 136.

[0050] Sample tray 110 is shown mounted to reference base 112. Reference base 112 may be a metal plate mounted to a heat treatment chamber frame (not shown) within sample manager 14. Reference base 112 may include an opening through which a deflection limiting post 120 extends. The deflection limiting post 120 may be configured to prevent sample tray 110 from deflecting more than a certain distance relative to reference base 112 before coming to a stop. The deflection limiting post 120 may be keyed to a channel in the bottom of sample tray 110 and may act as a bearing to allow sample tray 110 to rotate about reference base 112. Rotation of sample tray 110 about reference base 112 may be generated by a motor 150 disposed on reference base 112 near the periphery of sample tray 110. Reference base 112 also includes a plurality of threaded openings configured to receive bolts for attaching right-angle brackets 118 at each side. Right-angle brackets 118 may be configured to attach a vertical frame 114 to reference base 112 in a vertical orientation. An encoder (not shown) may be further attached to the sample disk 110 to maintain the positioning of the sample disk 110 relative to the reference base 112.

[0051] A vertical frame 114 is attached to a reference base 112 such that the vertical frame 114 extends through the circumference of the sample disk 110. Given that this location is above the sample disk 110, the vertical frame 114 includes an opening 140 (e.g., Figure 4 As shown in the diagram, or through a cutout, the sample tray 110 and any received sample vial carriers 124a, 124b, and any received sample vials 33 are configured to pass through this opening or cutout. The opening 140 is sized high enough to receive a tall sample vial holder 124b without causing interference. A vertical frame 114 forms a surface above the opening 140 on which the needle arm 116 is mounted.

[0052] The needle arm 116 is shown as including a drive mechanism 142 and a motor 144. The motor 144 is configured to rotate about the axis of a rotating belt 148, which in turn rotates a pulley 152. The rotation of the pulley 152 can be configured to cause the needle arm 116 to rotate about a second vertical axis A2. The rotation of the needle arm 116 can be an independent rotation relative to the rotation of the sample disk 110, and can be a rotation about a vertical axis A2 different from the vertical axis A1 around which the sample disk 110 rotates.

[0053] See now Figure 4 The first calibration position shows a configuration according to one embodiment. Figure 1 and Figure 2 A perspective view of the interior of the sample manager 14. Figure 4 The first calibration position shown is needle arm 116 relative to Figure 3The position shown is a position rotated counterclockwise about the second vertical axis A2. As shown, shaft 154 extends through pulley 152, which is attached to and configured to rotate with pulley 152. Shaft 154 is connected to a rotating plate 155, which is configured to rotate with shaft 154 and rotate needle assembly 190. Shaft 154 includes a bias spring 232. A removable needle arm housing 158 is attached to vertical frame 114. The removable needle arm housing 158 includes a horizontal plate 160 extending just above an opening 140 in vertical frame 114. Horizontal plate 160 includes a bushing 156 configured to receive the base of shaft 154 and maintain alignment of shaft 154 with the second vertical axis A2. Needle arm housing 158 is removably attached to vertical frame 114 by a plurality of accessible bolts 162. Accessible bolts 162 are accessible through door 130 of sample manager 14. This allows the entire vertical frame 114 and needle arm 116, along with all its components, to be easily removed through door 130 during maintenance or parts replacement.

[0054] The needle arm 116 also includes a magnetic encoder 146. The magnetic encoder 146 can be configured to determine the rotational position of the needle arm 116 to any tolerance required for accurate positioning of the sample needle 122. Similarly, the motor 150 can be equipped with an encoder for determining the rotational position of the sample tray 110. Both encoders in the system can communicate with a control system (e.g., data system 34) for calibrating and controlling the movement of the needle arm 116 and the sample tray 110. While magnetic encoders can be used, other encoders, such as optical encoders, are contemplated.

[0055] The needle arm 116 is shown as including two separate motors 164a and 164b, which are configured to rotate two separate drive shafts. The first motor 164a is configured to rotate the first drive shaft 236 (as shown in the image). Figure 6 and Figure 8 The first drive shaft rotates (as shown), moving on the puncture needle 122. The second motor 164b is configured to cause the second drive shaft 238 (as shown) to rotate. Figure 6 and Figure 8 The second drive shaft rotates, moving on the sample needle (not shown). A first motor 164a and a second motor 164b can be attached to the needle arm 116, such that motors 164a and 164b rotate together with the needle arm 116. The puncture needle 122 can be operated in conjunction with the sample needle to puncture any material or membrane covering the sample vial. The two motors 164a and 164b can be configured to operate independently and can be controlled and programmed by the control system and / or data system 34 for use in operating routines.

[0056] The needle assembly 190 of the needle arm includes a plate 192 with two accessible bolts 194, which are accessible to a technician who opens the door 130 of the sample manager 14. After loosening the accessible bolts 194, the technician can remove the needle assembly 190 and the attached motors 164a, 164b from the needle mechanism base 230. The needle assembly 190 and the motors 164a, 164b can be removed through the door 130 of the sample manager 14 without removing the needle mechanism base 230. Similarly, the motors 164a, 164b can be easily removed from the needle arm 116 by removing one or more accessible motor bolts 196 from the plate 192. This allows the motors 164a, 164b to be easily replaced or removed for maintenance through the front door 130 of the sample manager 14 without removing other parts of the needle arm 116.

[0057] The sample delivery system may also include a fluid tube (not shown) located between the sample needle and the liquid chromatography column 18. The fluid tube may include a coiled portion configured to extend and retract during rotation of the needle arm 116 about a second vertical axis A2. The coiled portion may extend between the top of the needle arm 116 above the puncture needle 122 and the vertical frame 114. The coiled portion may unfold as the needle arm 116 rotates away from the vertical frame 114 and retract as the needle arm 116 rotates toward the vertical frame 114. The coiled portion of the fluid tube may be helical, curved, or otherwise coiled to provide longitudinal extension and retraction in a predictable manner without interfering with other movements of the various components within the sample manager 14.

[0058] See again Figure 3 In this view, the needle arm 116 is shown rotated to its original position, whereby the protruding stop 182, connected to, coupled to, or integrated into the vertical frame 114, contacts the needle assembly 190. The original position can be a position where the needle arm 116 may not be able to rotate beyond a stopping point. As shown, in the original position, the needle arm 116 rotates clockwise to its maximum rotation point, whereby the protruding stop 182 stops the needle arm 116 from further clockwise rotation.

[0059] Attached to the reference base 112 may be a needle cleaning system (not shown) extending from an opening 170 in the reference base 112 located near its original position or location. The needle cleaning system may include multiple liquid source tubes, each configured to introduce water and / or other cleaning agents to clean the sample needle 122 and / or puncture needle as the needle moves over the needle cleaning system. The cleaning process may include, for example, providing a first cleaning agent to the sample needle 122 from a first liquid source tube, and then moving the sample needle 122 over a second liquid source tube to clean it with water. Other cleaning processes and configurations suitable for cleaning needles in the needle arm 116 are contemplated.

[0060] The needle arm 116 can be configured to rotate an amount about the rotation axis 154 and the second axis A2, such that the needle assembly 190 completely covers the entire working portion of the sample tray 110. In the illustrated embodiment, the needle arm 116 can be configured to rotate more than 45 degrees but less than 90 degrees. Additional rotational movements (i.e., equal to or greater than 90 degrees) in addition to the illustrated rotational movements are also contemplated in other embodiments.

[0061] See Figure 4 and Figure 5 This illustrates an implementation scheme. Figure 1 and Figure 2 The sample manager 14 is located inside, with the needle arm 116 positioned in two calibration positions. Various calibration systems are envisioned in various proposed implementations. Figure 4 and Figure 5 An exemplary calibration system is shown, wherein the data system 34 and / or the sample manager control system can be configured to calibrate the sampling mechanism 100 for use. A calibration process may include, for example... Figure 4 The first step, as shown, involves moving the sample tray 110 and needle arm 116 to align the needle with the first opening 210 in the sample tray, and then recording the first encoder position of each of the sample tray 110 and needle arm 116. For example, the needle arm 116 can be moved from its original position (e.g., Figure 3 (As shown) Move counterclockwise to Figure 4 The position shown allows the puncture needle 122 (or sample needle) to be positioned directly above the first opening 210.

[0062] The calibration process may then include moving the sample tray 110 and the needle arm 116 to... Figure 5 The second step, as shown, involves aligning the puncture needle 122 (or sample needle) with the second opening 220 in the sample tray. The calibration process can then include recording the second encoder position of each of the sample tray 110 and the needle arm 116. Using the known first and second encoder positions, the data system 34 and / or the sample manager control system can be configured to inversely calculate the geometric parameters of the sampling mechanism 100, thereby calibrating the movement and position of the sample tray 110 and the needle arm 116. Positional accuracy can be more precise than typical prior art calibration processes because the method of the present invention described above does not rely on the assumption that geometric quality is within a certain level of tolerance.

[0063] Figure 6A perspective view of a needle arm 116 detached from the interior of a sample manager 14 according to one embodiment is depicted. As shown, the needle arm 116 includes a base 230 removably attachable to the sample manager 14 of the liquid chromatography system 10. The needle arm 116 also includes a needle assembly 190 removably attached to the base 230. The removability of the base 230 from the sample manager 14 and the removability of the needle assembly 190 from the base 230 are each provided by accessible bolts, screws, pins, or other easily accessible, engageable, and / or detachable coupling devices. The attachable removability of each of these components, as described herein, provides ease of service and replacement of the components of the needle arm 116 through the front door of the sample manager 14. Furthermore, as described above, the needle arm 116 includes sufficient structure to provide rotational movement of the arm about a vertical axis when the needle arm 116 is attached within the sample manager 14.

[0064] Figure 7 The disassembly of the needle assembly 190 according to one embodiment is depicted. Figure 6 A perspective view of the base 230 of the needle arm. The base 230 includes a removable needle arm housing 158. The removable needle arm housing 158 provides a frame for attaching the base 230 to the interior of the sample manager 14 of the liquid chromatography system 10, such as by attaching the removable needle arm housing 158 to a vertical frame 114. The removable needle arm housing 158 includes a flat vertical surface configured to adjoin a flat vertical surface of the vertical frame 114. Figure 6 As shown, a plurality of alignment pins 234 located on the back surface of the needle arm housing 158 cooperate with accessible bolts 162 to attach the flat vertical surface of the needle arm housing 158 to the flat vertical surface of the vertical frame 114. Although not shown, the vertical frame 114 may include corresponding holes or concave receiving openings for receiving each of the accessible bolts 162 and alignment pins 234.

[0065] As shown in the figure, the base 230 includes a shaft 154 configured to rotate about a vertical axis A2. A removable needle arm housing 158 is configured to hold the shaft 154 in both a top and bottom position while allowing the shaft 154 to rotate about the removable needle arm housing 158. Specifically, the removable needle arm housing 158 includes a lower horizontal plate 160 and an upper horizontal plate 161 extending from a flat vertical surface of the removable needle arm housing 158. A bushing 156 has an opening in the lower horizontal plate 160, allowing the shaft 154 to rotate therein.

[0066] The base 230 also includes a motor 144, a drive mechanism 142, a belt 148, a pulley 152, and a rotating plate 155. The drive mechanism 142 of the motor 144 may be a drive shaft or similar component in which the motor 144 is configured to rotate. Rotation of the drive mechanism 142 further causes movement of the belt 148, thereby causing rotation of the pulley 152, which is attached to the vertical shaft 154. The rotating plate 155 is attached to the shaft 154 and is configured to rotate with the shaft 154.

[0067] Figure 8 A side view of a needle arm 116 according to one embodiment is depicted, the needle arm including both a needle assembly 190 and a base 230. See also Figure 6 Perspective view and Figure 8 The side view shows a base 230, which includes each of a motor 144, a magnetic encoder 146, a housing 158, and a rotating plate 155. The needle assembly 190 includes a housing 264 or other body to which components are attached. As shown, a plate 192 of the housing 264 of the needle assembly 190 is attached to the base 230 and specifically to the rotating plate 155.

[0068] The needle assembly 190 includes a drive system. The drive system includes a first motor having a first drive shaft 236 attached to the top of a plate 192 of the housing 264. The needle assembly 190 also includes a second motor 164b having a second drive shaft 238 attached to the bottom of the plate 192 of the housing 264. The first motor 164a and the first drive shaft 236 are configured to apply vertical movement or movement to the puncture needle 122 via applying vertical motion or movement along the puncture needle axis 260. Similarly, the second motor 164b and the second drive shaft 238 are configured to apply vertical movement or movement to the sample needle 261 via applying vertical motion or movement along the sample needle axis 258.

[0069] Furthermore, stripper leg 262 is attached to stripper leg axis 268, which includes a spring-loaded end 266 with a spring mechanism. The spring mechanism can be configured to compress during downward movement of stripper leg 262 and stripper leg axis 268. In use, stripper leg 262 can contact the top of a sample vial (not shown), after which a puncture needle 122 can be pushed through the protective membrane of the sample vial. After the puncture needle 122 has pierced this top protective membrane, the puncture needle 122 must retract from the sample vial and the protective membrane. Stripper leg 262 can be configured to provide a downward force on the top of the sample vial, such that the puncture needle 122 can retract properly without adhering to the protective membrane of the sample vial. Stripper leg 262 includes an opening through which the puncture needle 122 is configured to extend during puncture.

[0070] like Figure 6 As shown, the stripper leg axis 268 is movable relative to the puncture needle axis 260 via two connectors 270. The connectors 270 may include a top elongated vertical opening and a bottom elongated opening located in the stripper leg axis 268, with corresponding top and bottom pins extending through these openings. The corresponding top and bottom pins are attached to the puncture needle engagement surface 272 of the puncture needle axis 260. The top and bottom elongated vertical openings engage with the pins such that the stripper leg axis 268 and the puncture needle axis 260 are connected in a manner that allows vertical movement between them, or otherwise. The maximum vertical movement between the stripper leg axis 268 and the puncture needle axis 260 is defined by the vertical length of the top and bottom elongated vertical openings in the stripper leg axis 268.

[0071] The sample needle 261 is positioned along the same vertical axis as the puncture needle 122. The sample needle 261 may be a needle with a diameter smaller than that of the puncture needle 122, such that the sample needle 261 is configured to extend through a larger diameter opening in the puncture needle 122. A needle holder 244 is located at the top of the sample needle axis 258. The sample needle holder 244 may be configured to removably receive the sample needle 261 at a position where it is aligned with the puncture needle 122. The sample needle holder 244 is attached to the sample needle axis 258 such that the sample needle holder 244 and thus the sample needle 261 move when the sample needle axis 258 is driven or moved by the second motor 164b and its second drive shaft 238.

[0072] Figure 9 A top view of the needle arm 116 according to one embodiment is depicted. (Reference) Figure 6 Perspective and Figure 9 The top view of both shows the needle arm sensor system. The sensor system includes a sample needle origin sensor 240, a puncture needle origin sensor 254, and a top sensor 252. The sensor system may also include a printed circuit board 246 configured to provide power, control signals, and / or communication signals to / from the various sensors 240, 254, 252 in the sensor system. The printed circuit board 246 may be a flexible circuit board configured to bend as the needle assembly 190 rotates about a vertical axis 154. The printed circuit board 246 may be able to perform its function without sacrificing its signal and / or conductivity integrity while bending back and forth across the needle arm 116 throughout its lifespan due to the rotation of the needle assembly 190 about the vertical axis 154. The sensor system and / or the printed circuit board 246 and sensors 240, 254, 252 may be operatively communicateable with a control system such as a data system 34, such that sensed information is provided to the data system 34 for processing.

[0073] The sample needle origin sensor 240 is configured to sense movement of the sample needle axis 258 and / or determine when the sample needle axis 258 reaches its original (top) position. The sample needle origin sensor 240 may be configured to sense and / or determine that the sample needle 261 has moved a predetermined distance vertically to its original position. A sample needle holder 244 is connected to and moves with the sample needle axis 258. The sample needle holder 244 includes an extension protrusion 242 configured to move between the two prongs of the sample needle origin sensor 240. Thus, when the sample needle axis 258 moves to its top original position, the extension protrusion 242 is positioned between the two prongs of the sample needle origin sensor 240, thereby sensing that the sample needle axis 258 is in its original position. A connecting conductor 248 extends between a printed circuit board 246 and the sample needle origin sensor 240, which is configured to provide power and / or other control or communication signals to and from the sample needle origin sensor 240.

[0074] The needle origin sensor 254 is configured to sense movement of the needle axis 260 and / or determine when the needle axis 260 reaches its original (top) position. The needle origin sensor 254 can be configured to sense and / or determine that the needle 122 has moved a predetermined distance vertically to its original position. The needle axis 260, and specifically, its needle engagement surface 272, includes an extension protrusion 256 configured to move between two prongs of the needle origin sensor 254. Thus, when the needle axis 260 moves to its top original position, the extension protrusion 256 is positioned between the two prongs of the needle origin sensor 254, thereby sensing that the needle axis 260 is in its original position. A connecting conductor 248 extends between a printed circuit board 246 and the needle origin sensor 254, which is configured to provide power and / or other control or communication signals to and from the needle origin sensor 254.

[0075] The top sensor 252 of the sensor system is configured to sense when the stripper leg 262 is compressed by a predetermined amount. This predetermined amount may correspond to the force acting on the stripper leg 262 through the top of the sample vial. A service loop 250 extends from the printed circuit board 246 to the top sensor 252 to provide power and / or other control or communication signals to and from the top sensor 252. The top sensor 252 may be a stripper leg movement sensor configured to determine that the stripper leg 262 has moved a predetermined distance in the vertical direction.

[0076] Figure 10 Depicting the implementation of an scheme in Figure 9The figure shows a side cross-sectional view of the needle arm 116 taken at arrow 10-10. As shown, the drive system may include a system for converting the rotational motion of drive shafts 236, 238 into vertical linear motion of axes 258, 260. The first motor 164a and the second motor 164b can operate independently of each other, enabling the puncture needle 122 and the sample needle 261 to move vertically independently. The top drive shaft 236 is shown as an opening extending from the first motor 164a through a plate 192 of the housing 264. Similarly, the bottom drive shaft 238 is shown as an opening extending from the second motor 164b through a plate 192 of the housing 264. As shown, the top drive shaft 236 is attached to a coupling structure 274 configured to bypass the sample needle axis 258 and engage with the puncture needle axis 260 to convert the rotational motion of the drive shaft 236 into linear vertical motion of the puncture needle axis 260. Similarly, the bottom drive shaft 238 is attached to the engagement structure 276, which is configured to engage with the sample needle axis 258 to convert the rotational motion of the drive shaft 238 into the linear vertical motion of the sample needle axis 258.

[0077] Although the invention has been shown and described with reference to specific embodiments, those skilled in the art will understand that various changes in form and detail may be made without departing from the spirit and scope of the invention as set forth in the appended claims.

Claims

1. A liquid chromatography sample manager, the liquid chromatography sample manager comprising: Heat treatment chamber; A sample tray, which is mounted in the heat treatment chamber, is configured to rotate about a first vertical axis; A needle arm is mounted in the heat treatment chamber and is configured to rotate about a second vertical axis, wherein the combination of the rotation of the needle arm and the rotation of the sample disk is configured to provide complete coverage of the needle arm over the entire working portion of the sample disk. as well as A sample delivery system in fluid communication with a solvent delivery system, the sample delivery system including a sample needle attached to the needle arm, the sample delivery system being configured to transfer a first sample from a first sample vial holder located in the sample tray into a chromatographic flow stream.

2. The liquid chromatography sample manager of claim 1, further comprising a front door configured to load and unload a sample vial holder into the sample tray, wherein the needle arm is removable from the front door.

3. The liquid chromatography sample manager according to claim 2, wherein the needle arm includes a belt and pulley drive mechanism.

4. The liquid chromatography sample manager of claim 3, wherein the heat treatment chamber further includes a motor operatively connected to the belt and pulley drive mechanism, wherein the motor is removable from the front door.

5. The liquid chromatography sample manager of claim 2, wherein the needle arm includes a magnetic encoder configured to determine the rotational position of the needle arm.

6. The liquid chromatography sample manager of claim 1, wherein the sample delivery system includes a fluid tube located between the sample needle and the liquid chromatography column, wherein the fluid tube includes a coiled portion configured to extend and retract during rotation of the needle arm.

7. The liquid chromatography sample manager according to claim 1, wherein the sample disk is circular and includes a first compartment, a support compartment, a support compartment, and a support compartment equidistantly arranged around the periphery of the sample disk.

8. The liquid chromatography sample manager of claim 1, further comprising a control system configured to control rotational movement of each of the sample disk and the needle arm, the control system configured to control a calibration process comprising the following steps: Move the sample tray so that the first opening in the sample tray is aligned with the sample needle on the needle arm; Move the needle arm above the aligned first opening and record the first encoder position of each of the sample tray and the needle arm; Move the sample tray so that the second opening in the sample tray is aligned with the sample needle on the needle arm; Move the needle arm above the aligned second opening and record the second encoder position of each of the sample tray and the needle arm; as well as Using the known positions of the first encoder and the second encoder, the geometric parameters of the sample disk and the needle arm are calculated to calibrate the movement of the sample disk and the needle arm.

9. The liquid chromatography sample manager of claim 1, wherein the needle arm is configured to rotate at least 45 degrees about the second vertical axis, and wherein the sample disk is configured to rotate 360 ​​degrees about the first vertical axis.

10. A liquid chromatography system, the liquid chromatography system comprising: Solvent delivery system; Liquid chromatography sample manager according to any one of claims 1-9; A liquid chromatography column, wherein the liquid chromatography column is located downstream of the solvent delivery system and the sample delivery system; as well as A detector located downstream of the liquid chromatography column.

11. A method for calibrating a liquid chromatography sample manager according to any one of claims 1-9, the method comprising: Move the sample tray so that the first opening in the sample tray is aligned with the sample needle on the needle arm; Move the needle arm above the aligned first opening and record the first encoder position of each of the sample tray and the needle arm; Move the sample tray so that the second opening in the sample tray is aligned with the sample needle on the needle arm; Move the needle arm above the aligned second opening and record the second encoder position of each of the sample tray and the needle arm; as well as Using the known positions of the first and second encoders, the geometric parameters of the sample disk and the needle arm are calculated to calibrate the movement of the sample disk and the needle arm.

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